We propose to define the prostaglandin synthetic and degradative capabilities of different segments of the mammalian nephron in health and disease. Specifically, we will isolate glomeruli, cortical tubules and medullary collecting tubules from normal animals and animals with hypertension or ureteral obstruction. Additionally, cell cultures will be established from glomeruli and collecting tubules. Synthetic capabilities for arachidonate end products will be assessed by radioimmunoassay, radiometric thin-layer chromatography, platelet aggregation assay, high pressure liquid chromatography and gas chromatography - mass spectroscopy. These same techniques will allow quantitation of the prostaglandin degradative capacity of the nephron segments. Cell culture strains of glomerular and collecting tubular cells will permit further definition of the profile of prostaglandins produced by the nephron. Using nephron segments or cell culture, we wish to evaluate the following possible stimuli of prostaglndin or thromboxane synthesis: bradykinin, angiotensin II, vasopressin, parathyroid hormone, adrenergic agonists, calcium and histamine. Using Kyoto spontaneously hypertensive rats, we wish to measure glomerular synthesis of PGI-2 before and after antihypertensive therapy. Using rats, we will evaluate prostaglandin and thromboxane production in nephron segments after varying periods of ureteral obstruction with and without pretreatment with 1-benzyl-imidazole or tranylcypromine. In cell cultures of collecting tubular epithelia, we will assess the role of prostaglandins in mediating responsiveness of adenylate cyclase to vasopressin. In cell cultures of glomeruli, we will measure renin production, its stimulability by prostaglandins and the correlations between renin release and prostaglandin production.